tbuckley/cabot-search huggingface dataset:
Topical steroid withdrawal syndrome: time to bridge the gap
Authors: Chantal Cotter, Tim Burton, Andrew Proctor, Celia Moss, Carsten Flohr
Journal: British Journal of Dermatology (2022)

Since their introduction in the 1950s, topical corticosteroids (TCSs) have improved the lives of many dermatology patients. In 2020–2021, over 10·5 million tubes of TCSs were prescribed in England alone1 and in addition, many more were purchased over the counter. Yet in 2021 the Medicines and Healthcare products Regulatory Agency issued a new warning on TCSs, advising patients to seek medical advice if skin burning or redness occurs after discontinuing treatment.2 What has led to this new caution surrounding one of dermatology's most relied resources? There is growing public awareness and concern about Topical Steroid Withdrawal Syndrome (TSWS), also known as Topical Steroid Addiction or Red Skin Syndrome. A systematic review by Hwang and Lio 3 describes TSWS as a distinct clinical entity of skin burning and erythema, which occurs most frequently in women, sometimes in under 18‐year‐olds, after discontinuation of prolonged application of moderate‐to‐high potency TCSs.3 This review also highlights the poor quality of research that has been completed in TSWS.
Treatment of Adults With Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia—From Intensive Chemotherapy Combinations to Chemotherapy-Free Regimens
Authors: Elias Jabbour, Fadi G. Haddad, Nicholas J. Short, Hagop Kantarjian
Journal: JAMA Oncology (2022)

Importance With the advent of potent BCR::ABL1 tyrosine kinase inhibitors (TKIs), Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) is now a relatively favorable-risk acute leukemia. In this review, we discuss the current evidence for frontline therapies of Ph-positive ALL, the major principles that guide therapy, and the progress with chemotherapy-free regimens. Observations Incorporating TKIs into the chemotherapy regimens of patients with newly diagnosed Ph-positive ALL has led to improved remission rates, higher probability of reaching allogeneic stem cell transplantation (SCT), and longer survival compared with chemotherapy alone. Early achievement of a complete molecular remission (CMR) is an important end point in Ph-positive ALL and identifies patients who have excellent long-term survival and may not need allogeneic SCT. Second-generation TKIs combined with intensive or low-intensity chemotherapy resulted in higher CMR rates compared with imatinib-based regimens. This translated into better outcomes, with less reliance on allogeneic SCT. To further improve the outcomes, the potent third-generation TKI ponatinib was added to chemotherapy. The combination of hyper-CVAD and ponatinib resulted in an overall CMR rate of 84% and a 5-year survival rate of 73% and 86% among patients who did and did not undergo allogeneic SCT, respectively, suggesting that allogeneic SCT may not be needed with this regimen. The recent chemotherapy-free combination of dasatinib and blinatumomab was safe and effective in patients with newly diagnosed Ph-positive ALL and resulted in an estimated 3-year OS rate of 80%; 50% of patients underwent allogeneic SCT. The chemotherapy-free regimen of ponatinib and blinatumomab resulted in a CMR rate of 86% and a 2-year survival rate of 93%, with no relapses or leukemia-related deaths, and with only 1 patient proceeding to allogeneic SCT. Conclusions and Relevance The promising results obtained with the chemotherapy-free regimens of blinatumomab plus TKIs question the role of allogeneic SCT in first remission. Patients with Ph-positive ALL who achieve early and deep molecular responses have excellent long-term outcomes and may not benefit from allogeneic SCT.
Artificial Intelligence and the Promise of Expediting and Standardizing the Reviewing and Reporting of Capsule Endoscopy Videos
Authors: Michael Sey
Journal: JAMA Network Open (2022)

Xia Xie, MD, PhD; Yu-Feng Xiao, MD, PhD; Xiao-Yan Zhao, MD, PhD; Jian-Jun Li, MB; Qiang-Qiang Yang, MM; Xue Peng, MB; Xu-Biao Nie, MM; Jian-Yun Zhou, MD, PhD; Yong-Bing Zhao, MM; Huan Yang, MM; Xi Liu, MD, PhD; En Liu, MD, PhD; Yu-Yang Chen, MM; Yuan-Yuan Zhou, MM; Chao-Qiang Fan, MM; Jian-Ying Bai, MD, PhD; Hui Lin, MD, PhD; Anastasios Koulaouzidis, MD, DM, PhD; Shi-Ming Yang, MD, PhD
Tom Nolan’s research reviews—7 July 2022
Authors: Tom Nolan
Journal: BMJ (2022)

Injuries account for nearly 1 million lives lost each year to children under the age of 18 years. In addition to deaths, millions of children each year sustain disability because of injuries. As disability adjusted life years lost from communicable diseases and perinatal causes are reduced, the global burden of injuries will increase. Prevention and control of injuries is an important component of child survival and improving child health globally, although less than 1% of the global health budget is spent on injury control. The armamentarium to address the problem of injuries is large, and solutions to child and adolescent injury control can be achieved though a combination of adaptation of these methods to the local environment and development of new, context specific interventions. The full spectrum of injury control must be employed, encompassing primary prevention, acute care of the injured patient, and rehabilitation to return the injured child as a functioning member of the community. Application of five readily available interventions could decrease child injury deaths by 30% and save 275 000 lives each year. If global child injury death rates in low and middle income countries were the same as in LMIC in South America, 439 000 lives would be saved annually, a decrease from current levels of 46%. Interdisciplinary collaboration within and across countries is critical in accomplishing these goals.
Response to the clinical commentary ‘Telemedical monitoring by an implanted loop recorder: gateway to personalized medicine? Results of the SMART-MI study’
Authors: Konstantinos D Rizas, Stefan Kääb, Steffen Massberg, Axel Bauer
Journal: Cardiovascular Research (2022)

To the editor: With great interest we read the commentary1 on our SMART-MI-DZHK9 study2 in the journal. We agree with the main conclusion of the authors that ‘telemedical care can bring personalized medicine closer’. However, we believe that several important aspects of the comment require clarification. One, the authors criticize an apparently low inclusion rate of only ‘three patients per year per centre’. However, the authors do not consider that in our study, as in most other trials, centres were not activated simultaneously. Moreover, our study enrolled a total of 1305 study participants who provided informed consent and underwent risk stratification by biosignal analysis, of which 400 high-risk patients took part in the randomized part of the study. This translates into an enrolment rate of 17 patients per year per centre. We consider this a major achievement for an investigator-initiated, publicly funded study with comparatively low patient fees...
Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer
Authors: Amanda N. Ruggieri, Mark Yarchoan, Subir Goyal, Yuan Liu, Elad Sharon, Helen X. Chen, Brian M. Olson, Chrystal M. Paulos, Bassel F. El-Rayes, Shishir K. Maithel, Nilofer S. Azad, Gregory B. Lesinski
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Biliary tract cancers (BTC) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibition (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC. Experimental Design: We examined immune features in peripheral blood from 77 patients with advanced BTC enrolled in a phase II clinical trial investigating atezolizumab with or without cobimetinib. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from whole blood to evaluate soluble factors and immune cell populations. Baseline blood samples were additionally compared with healthy donors to identify immune signatures unique to BTC. Results: At baseline, the soluble factors platelet-derived growth factor B (PDGF)-BB, placental growth factor (PlGF)-1, IL5, and IL17A were elevated in patients with BTC compared with healthy adult donors, and higher baseline frequencies of CD8+BTLA+ T cells correlated with better overall survival (OS) in this trial. There were also significant treatment-related alterations in several factors, including decreased PDGF-BB following combination treatment, that correlated with improved OS and progression-free survival (PFS). Higher baseline levels of IL23 and RANTES corresponded to improved clinical outcomes following combination treatment. Dual MEK/PD-L1 inhibition increased populations of CD4+TIM3+ and decreased CD8+VISTA+ T cells, correlating with worse OS and better PFS, respectively. Conclusions: This work represents a comprehensive analysis of peripheral immune features in patients with BTC and systemic responses to dual MEK/PD-L1 inhibition. These data support further investigation to understand how MEKi combines with immunotherapeutic approaches to improve clinical outcomes for patients with advanced BTC.
National Trends in the Achievement of Recommended Strategies for Stroke Prevention in U.S. Adults With Type 2 Diabetes, 2001–2018
Authors: Shihchen Kuo, Chun-Ting Yang, William H. Herman, Lynda D. Lisabeth, Wen Ye
Journal: Diabetes Care (2022)

To assess the national prevalence of and trends in achieving current guideline-recommended treatment goals and pharmacotherapies for primary and secondary prevention of stroke among U.S. adults with type 2 diabetes (T2D).We performed serial cross-sectional analyses in 4,834 adults aged ≥45 years with T2D who participated in the 2001-2018 National Health and Nutrition Examination Survey. With stratification by stroke history, we estimated the proportion of adults with T2D who achieved current guideline-recommended strategies for stroke prevention. Preventive strategies for stroke were benchmarked against diabetes care and cardiovascular risk reduction guidelines.Overall in 2001-2018, among those without stroke history, the proportion who achieved primary stroke prevention strategies ranged from 8.4% (95% CI 6.8-10.1) for aspirin/clopidogrel treatment in those with a higher cardiovascular disease risk to 80.5% (78.8-82.2) for nonsmoking. Among those with stroke history, the proportion who achieved secondary stroke prevention strategies ranged from 11.8% (8.7-14.8) for weight control to 80.0% (74.9-84.9) for glycemic control. From 2001 to 2018, among those without stroke history, there was a significant increase in statin therapy (Ptrend < 0.0001), smoking abstinence (Ptrend = 0.01), and ACE inhibitor/angiotensin receptor blocker treatment for hypertension (Ptrend = 0.04) but a substantial decline in weight control (Ptrend < 0.001). Among those with stroke history, only statin therapy (Ptrend = 0.01) increased significantly over time.During 2001-2018, the achievement of some current guideline-recommended strategies for stroke prevention among U.S. adults with T2D improved but remains a challenge overall. Efforts are needed to improve implementation of strategies for stroke prevention in this population.
Comparison of Patient Outcomes Before and After Switching From Warfarin to a Direct Oral Anticoagulant Based on Time in Therapeutic Range Guideline Recommendations
Authors: Brian Haymart, Geoffrey D. Barnes, Xiaowen Kong, Mona Ali, Eva Kline-Rogers, Deborah DeCamillo, Scott Kaatz
Journal: JAMA Network Open (2022)

This cohort study evaluates stroke and major bleeding rates before and after switching from warfarin to a direct oral anticoagulant (DOAC) in patients grouped by pre-switch time-in-therapeutic range guideline thresholds.
Risk of Mild Cognitive Impairment or Probable Dementia in New Users of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors
Authors: Jordana B. Cohen, Zachary A. Marcum, Chong Zhang, Catherine G. Derington, Tom H. Greene, Lama Ghazi, Jennifer S. Herrick, Jordan B. King, Alfred K. Cheung, Nick Bryan, Mark A. Supiano, Joshua A. Sonnen, William S. Weintraub, Daniel Scharfstein, Jeff Williamson, Nicholas M. Pajewski, Adam P. Bress
Journal: JAMA Network Open (2022)

<h3>Importance</h3> The cardiovascular and renal outcomes of angiotensin-II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatment are well-known; however, few studies have evaluated initiation of these agents and cognitive impairment. <h3>Objective</h3> To emulate a target trial to evaluate the cognitive outcomes of initiating an ARB- vs ACEI-based antihypertensive regimen in individuals at risk for mild cognitive impairment (MCI) and probable dementia (PD). <h3>Design, Setting, and Participants</h3> Active comparator, new-user observational cohort study design using data from the Systolic Blood Pressure Intervention Trial (SPRINT), conducted November 2010 through July 2018. Marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions were estimated with inverse probability (IP) weighting to account for confounding. Participants were using neither an ARB nor ACEI at baseline. Data analysis was conducted from April 7, 2021, to April 26, 2022. <h3>Exposures</h3> New users of ARB vs ACEI during the first 12 months of trial follow-up. <h3>Main Outcomes and Measures</h3> Composite of adjudicated amnestic MCI or PD. <h3>Results</h3> Of 9361 participants, 727 and 1313 new users of an ARB or ACEI, respectively, with well-balanced baseline characteristics between medication exposure groups after inverse probability weighting (mean [SD] age, 67 [9.5] years; 1291 ]63%] male; 240 [33%] Black; 89 [12%] Hispanic; 383 [53%] White; and 15 [2%] other race or ethnicity. In the primary analysis, during a median follow-up of 4.9 years, the inverse probability–weighted rate of amnestic MCI or PD was 4.3 vs 4.6 per 100 person-years among participants initiating ARB vs ACEI (HR, 0.93; 95% CI, 0.76-1.13). In subgroup analyses, new users of an ARB vs ACEI had a lower rate of amnestic MCI or PD among those in the standard systolic blood pressure treatment arm (HR, 0.61; 95% CI, 0.41-0.91) but not in the intensive arm (HR, 1.17; 95% CI, 0.90-1.52) (<i>P</i> = .007 for interaction). <h3>Conclusions and Relevance</h3> In this observational cohort study of US adults at high cardiovascular disease risk, there was no difference in the rate of amnestic MCI or PD among new users of an ARB compared with ACEI, although 95% CIs were wide.
Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study
Authors: Caroline Houillier, Sylvain Dureau, Luc Taillandier, Roch Houot, Olivier Chinot, Cécile Moluçon-Chabrot, Anna Schmitt, Rémy Gressin, Sylvain Choquet, Gandhi Damaj, Frédéric Peyrade, Julie Abraham, Vincent Delwail, Emmanuel Gyan, Laurence Sanhes, Jérôme Cornillon, Reda Garidi, Alain Delmer, Ahmad Al Jijakli, Pierre Morel, Agathe Waultier, Jérôme Paillassa, Adrien Chauchet, Thomas Gastinne, Mouna Laadhari, Anne-Sophie Plissonnier, Loïc Feuvret, Nathalie Cassoux, Valérie Touitou, Damien Ricard, Khê Hoang-Xuan, Carole Soussain
Journal: Journal of Clinical Oncology (2022)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively (P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio, 0.13; P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.
Raspberry Ice Cream
Authors: Lindsay L. Puckett
Journal: JAMA Oncology (2022)

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Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries
Authors: A. Rouf Banday, Megan L. Stanifer, Oscar Florez-Vargas, Olusegun O. Onabajo, Brenen W. Papenberg, Muhammad A. Zahoor, Lisa Mirabello, Timothy J. Ring, Chia-Han Lee, Paul S. Albert, Evangelos Andreakos, Evgeny Arons, Greg Barsh, Leslie G. Biesecker, David L. Boyle, Mark S. Brahier, Andrea Burnett-Hartman, Mary Carrington, Euijin Chang, Pyoeng Gyun Choe, Rex L. Chisholm, Leandro M. Colli, Clifton L. Dalgard, Carolynn M. Dude, Jeff Edberg, Nathan Erdmann, Heather S. Feigelson, Benedito A. Fonseca, Gary S. Firestein, Adam J. Gehring, Cuncai Guo, Michelle Ho, Steven Holland, Amy A. Hutchinson, Hogune Im, Les’Shon Irby, Michael G. Ison, Naima T. Joseph, Hong Bin Kim, Robert J. Kreitman, Bruce R. Korf, Steven M. Lipkin, Siham M. Mahgoub, Iman Mohammed, Guilherme L. Paschoalini, Jennifer A. Pacheco, Michael J. Peluso, Daniel J. Rader, David T. Redden, Marylyn D. Ritchie, Brooke Rosenblum, M. Elizabeth Ross, Hanaisa P. Sant Anna, Sharon A. Savage, Sudha Sharma, Eleni Siouti, Alicia K. Smith, Vasiliki Triantafyllia, Joselin M. Vargas, Jose D. Vargas, Anurag Verma, Vibha Vij, Duane R. Wesemann, Meredith Yeager, Xu Yu, Yu Zhang, Steeve Boulant, Stephen J. Chanock, Jordan J. Feld, Ludmila Prokunina-Olsson
Journal: Nature Genetics (2022)

Abstract The chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European ( n = 2,249) and African ( n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.
Sixty seconds on . . . the end of hangovers?
Authors: Luke Taylor
Journal: BMJ (2022)

<h3>Background:</h3> A systematic review of clinical decision rules to identify patients at low risk for community-acquired pneumonia (CAP) has not been previously presented in the literature. <h3>Methods:</h3> A systematic review of MEDLINE for prospective studies that used at least 2 signs, symptoms, or point-of-care tests to determine the likelihood of CAP. We included studies that enrolled adults and adolescents in the outpatient setting where all or a random sample of patients received a chest radiograph as the reference standard. We excluded retrospective studies and studies that recruited primarily patients with hospital-acquired CAP. <h3>Results:</h3> Our search identified 974 articles, 12 of which were included in the final analysis. The simple heuristic of normal vital signs (temperature, respiratory rate, and heart rate) to identify patients at low risk for CAP was reported by 4 studies and had a summary estimate of the negative likelihood ratio (LR−) of 0.24 (95% CI, 0.17 to 0.34) and a sensitivity of 0.89 (95% CI, 0.79 to 0.94). The simple heuristic of normal vital signs combined with a normal pulmonary examination to identify patients at low risk for CAP was reported by 3 studies, and had a summary estimate of LR− of 0.10 (95% CI, 0.07 to 0.13) with an area under the receiver operating characteristic curve of 0.92. <h3>Conclusions:</h3> Adults with an acute respiratory infection who have normal vital signs and a normal pulmonary examination are very unlikely to have CAP. Given a baseline CAP risk of 4%, these patients have only a 0.4% likelihood of CAP.